Carrageenan-induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis
Carrageenan-induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis
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DOI：
10.1002/eji.201545520
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发表时间：
2016-04-01
影响因子：
5.4
通讯作者：
Donadio, Marcio V. F.
中科院分区：
文献类型：
--
作者：
Barth, Cristiane R.;Funchal, Giselle A.;Donadio, Marcio V. F.
中性粒细胞胞外陷阱（NETs）是DNA纤维和颗粒蛋白质（如中性粒细胞弹性蛋白酶（NE））的组合。NET响应于不同的刺激而在细胞外空间中释放。角叉菜胶是一种从角叉菜（Chondrus crispus）中提取的硫酸化多糖，一种海藻，数十年来一直用于研究其在不同动物模型中诱导炎症的潜力。在这项研究中，我们首次表明，角叉菜胶注射可以诱导NET释放急性腹膜炎的小鼠模型。角叉菜胶诱导活性中性粒细胞释放NET，NE和髓过氧化物酶（MPO）表达在DNA纤维上。此外，尽管这种多糖能够刺激腹膜中性粒细胞产生活性氧（ROS），但NADPH氧化酶衍生的ROS被角叉菜胶抑制NET形成。总之，我们的研究结果表明，角叉菜胶诱导的小鼠腹膜炎症可以诱导NET的形成在一个ROS独立的方式。这些结果可能为炎症领域增加重要信息，并可能导致针对NET生产的新型抗炎剂。
Neutrophil extracellular traps (NETs) are a combination of DNA fibers and granular proteins, such as neutrophil elastase (NE). NETs are released in the extracellular space in response to different stimuli. Carrageenan is a sulfated polysaccharide extracted from Chondrus crispus, a marine algae, used for decades in research for its potential to induce inflammation in different animal models. In this study, we show for the first time that carrageenan injection can induce NET release in a mouse model of acute peritonitis. Carrageenan induced NET release by viable neutrophils with NE and myeloperoxidase (MPO) expressed on DNA fibers. Furthermore, although this polysaccharide was able to stimulate reactive oxygen species (ROS) generation by peritoneal neutrophils, NADPH oxidase derived ROS were dispensable for NET formation by carrageenan. In conclusion, our results show that carrageenan-induced inflammation in the peritoneum of mice can induce NET formation in an ROS-independent manner. These results may add important information to the field of inflammation and potentially lead to novel anti-inflammatory agents targeting the production of NETs.